PROJECT SUMMARY The overall goal of the Pluripotent Stem Cell and Organoid Core of the Digestive Health Center (DHC) is to provide new, cutting edge technologies that are focused on digestive disease research and enable the use of tissue organoids to model human disease. The Core pursues this goal with four complementary aims. In the first aim ?to provide DHC investigators with quality tested PSCs and PSC-derived GI tissues,? the Core makes available to users quality-tested human pluripotent stem cells (PSCs) and PSC-derived intestinal and gastric organoids. These are novel 3D-miniature organs that enable studies related to physiology and pathobiology relevant to humans. In the second aim ?to generate biopsy-derived human enteroids for DHC investigators,? the Core also provides investigators with the opportunity to generate gastric, intestinal, and colonic ?enteroids? from healthy or diseased subjects. In the third aim ?to derive and quality test disease-specific induced PSC,? the Core applies well-established transfection, culture, and phenotyping protocols to generate inducible PSCs (iPSCs) from normal and diseased subjects to facilitate studies of pathogenesis of disease, drug screening, etc. To be able to track and visualize these cells in experimental assays, the Core also provide PSC-editing and screening services to establish novel cell lines based on investigators' needs. And in the fourth aim ?to sponsor training courses and workshops on PSC and organoid technology,? the Core holds regular sessions on basic and advanced techniques for PSC culture, generation of iPSCs, and generation and use of human digestive tissue organoids. These novel technologies empower DHC investigators to study mechanisms of disease using multi-cellular experimental systems that have direct ?lineage? to normal and diseased human tissues (including at different stages of maturation). The delivery of services is streamlined and centralized, and positions investigators to explore new collaborative projects.